Table 1 Characteristics of included studies and patients
Kuisma et al. (2006) | HOT or NOT 2014 | EXACT PILOT 2018 | COMACARE 2018 | ICU-ROX substudy 2020 | BOX 2022 | EXACT 2022 | HOT-ICU substudy 2023 | ||
|---|---|---|---|---|---|---|---|---|---|
Study characteristics | |||||||||
Study period and location | -,Finland | 10/2012–09/2013, New Zealand | 07/2015–05/2017 Australia | 03/2016–11/2017 Finland, Denmark | 09/2015–05/2018 Australia, New Zealand | 03/2017–12/2021 Denmark | 12/2017–08/2020 Australia | 06/2017–08/2020, international trial | |
Study design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | RCT, multi-centric, single-blind design | |
Interventional strategy “Restrictive” | FiO2 30% for 60 min after ROSC, manual ventilation | Titrated oxygen therapy at mechanical ventilation, Sp02 90–94% or Fi02 0.4, until 72 h after randomization or extubation; start on scene | Titrated oxygen therapy 2L/min (4L/min at one study site), application through bag-valve reservoir | Normoxia, 10-15 kPa delivered by invasive mechanical ventilation, for 36 h after ICU arrival or until extubation or until spontaneous breathing, SpO2 target 95–98% | Titrated oxygen therapy aiming at FiO2 21%, lower SpO2 alarm at 90%, upper SpO2 alarm at 97%, treatment until ICU discharge or 28 days from randomization | PaO2 of 9–10 kPa delivered by invasive mechanical ventilation | Titrated oxygen therapy with target SpO2 90–94%, application through bag-valve reservoir 4L/min or mechanical ventilation (FiO2 0.6) until hospital arrival | PaO2 of 8 kPa delivered by invasive or non-invasive mechanical ventilation, up to 90 days | |
Comparator treatment “High-dose” | FiO2 100% for 60 min after ROSC, manual ventilation | Standard oxygen therapy at mechanical ventilation, Sp02 > 95%, until 72 h after randomization or extubation; start on scene | Standard oxygen therapy 10L/min (4L/min at one study site), application through bag-valve reservoir | Hyperoxia, 20-25 kPa delivered by invasive mechanical ventilation, for 36 h after ICU arrival or until extubation or until spontaneous breathing, | Standard oxygen therapy, lower SpO2 alarm at 90%, no upper SpO2 alarm. FiO2 < 30% was discouraged, treatment until ICU discharge or 28 days from randomization | PaO2 of 13–14 kPa delivered by invasive mechanical ventilation | Titrated oxygen therapy with target SpO2 98–100%, application through bag-valve reservoir 10L/min or mechanical ventilation (FiO2 1.0) until hospital arrival | PaO2 of 12 kPa delivered by invasive or non-invasive mechanical ventilation, up to 90 days | |
Start of intervention | Prehospital setting | Prehospital setting | Prehospital setting | ICU setting | ICU setting | ICU setting/ED | Prehospital setting | ICU setting | |
Number of patients enrolled | 32 | 18 | 62 | 123 | 166 | 802 | 425 | 335 | |
Cohort | Witnessed OHCA with VF | OHCA with presumed cardiac cause and VT/VF arrest | OHCA with presumed cardiac cause and VT/VF arrest | OHCA with presumed cardiac cause and VT/VF arrest | OHCA/IHCA from any origin and suspected hypoxic ischaemic encephalopathy | OHCA with presumed cardiac cause | OHCA with presumed cardiac cause | OHCA or IHCA from any origin | |
TTM | At treating physician’s discretion | Mandatory therapeutic hypothermia | At treating physician’s discretion | Mandatory TTM at either 33 °C or 36 °C | At treating physician’s discretion | Mandatory TTM at 36 °C | At treating physician’s discretion | - | |
Primary outcome | Survival to hospital discharge | Sp02 in pre-hospital period | Sp02 ≥ 94% at hospital arrival, proportion of patients | NSE serum concentration | Composite: death or unfavorable neurological outcome at 180 days | Composite: death or CPC score > 2 | Survival to hospital discharge | All-cause mortality at 90 days | |
Main secondary outcomes | Blood gases, Need to raise FiO2, Biomarker testings | SpO2 serially measured, PaO2, Hypoxemic episodes (Sp02 < 88%), survival to hospital discharge | Sp02 ≥ 90% at hospital arrival, Re-arrest, Survival to hospital discharge | Blood gases, Biomarker concentrations, Regional fronto cerebral oxygenation, EEG, favorable neurological outcome (CPC score ≤ 2) at 6 months, ICU length of stay, hospital length of stay, 30-day survival, serious adverse events | Mortality: ICU, in-hospital, 180 days, ICU length of stay, hospital length of stay, ventilator-free days, vasopressor-free days | Time to death, Discharge with CPC score > 2, vasopressor use, Biomarker testings, cognitive assessment, adverse events | Re-arrest before ICU arrival, Hypoxemia (< 90%) before ICU arrival, Survival to ICU discharge, ICU length of stay, Hospital length of stay, favorable neurological outcome (CPC score ≤ 2) at hospital discharge, SAE 12 months survival 12 months QoL | Days alive without life support, Days alive and out of hospital, SAE at ICU 1-year survival QoL | |
Baseline characteristics of patients included | |||||||||
Restrictive group | Patients | 14 | 8 | 37 | 61 | 87 | 394 | 214 | 149 |
High-dose group | Patients | 14 | 9 | 24 | 59 | 79 | 395 | 211 | 186 |
Restrictive group | Age, median | 61.9 (13.6) | 71.6 (10.7) Mean | 64 (13.5) Mean | 59 (13) Mean | 62.3 (14.8) Mean | 62 (13) | 66.4 | 70 |
High-dose group | Age, median | 64.3 (7.8) | 61.4 (20.8) Mean, SD | 60.5 (9) Mean, SD | 60 (14) Mean | 60.6 (16.1) Mean | 63 (14) | 64.2 | 71 |
Restrictive group | Male patients | 13/14 | 7/8 | 32/37 | 50/61 | 66/87 | 325/394 | 163/214 | 92/149 |
High-dose group | Male patients | 10/14 | 9/9 | 17/24 | 48/59 | 62/79 | 312/395 | 162/211 | 138/186 |
Restrictive group | Shockable rhythm | 14/14 | 8/8 | 37/37 | 61/61 | 58/87 | 334/393 | 128/214 | – |
High-dose group | Shockable rhythm | 14/14 | 9/9 | 24/24 | 59/59 | 46/79 | 333/394 | 135/211 | – |
Restrictive group | Witnessed CA | 14/14 | 6/8 | 27/37 | 61/61 | 72/87 | 333/394 | 166/214 | – |
High-dose group | Witnessed CA | 14/14 | 6/9 | 18/24 | 59/59 | 61/79 | 339/394 | 169/211 | – |
Restrictive group | Bystander CPR | 10/14 | 6/8 | 31/37 | 50/61 | 65/87 | 346/388 | 163/214 | – |
High-dose group | Bystander CPR | 6/14 | 7/9 | 23/24 | 48/59 | 56/79 | 333/388 | 157/211 | – |
Restrictive group | Collapse to ROSC, min, median | 17.4 (5.8) | 28.6 (12.6) | 18.5 | 20 | 26.5 (17.8) Mean | 21 (13) | 27.0 | – |
High-dose group | Collapse to ROSC, min, median | 20.4 (5.7) | 30.8 (16.3) | 19.5 | 21 | 25.4 (14.7) Mean | 21 (14) | 25.0 | – |
Restrictive group | Invasive mechanical ventilation | – | – | – | 61/61 | 87 | 394/394 | 157/214 | 142/149 |
High-dose group | Invasive mechanical ventilation | – | – | – | 59/59 | 79 | 395/395 | 159/211 | 175/186 |
Restrictive group | Vasopressors | 7/14 | – | – | – | 33/87 | 359/394 | – | 11/149 |
High-dose group | Vasopressors | 7/14 | – | – | – | 34/79 | 367/395 | – | 11/186 |
Restrictive group | TTM | 6/14 | 8/8 | – | 61/61 | 72/87 | 394/394 | 190/214 | – |
High-dose group | TTM | 8/14 | 8/9 | – | 59/59 | 65/79 | 395/395 | 186/211 | – |